Hisham S Alrubaye,Sarah M Reilly,Rafaela da Silva,NyJaee Washington,Jon P Boyle
{"title":"A single-cell atlas of Toxoplasma sexual development in the feline intestinal tract.","authors":"Hisham S Alrubaye,Sarah M Reilly,Rafaela da Silva,NyJaee Washington,Jon P Boyle","doi":"10.1038/s41564-026-02294-7","DOIUrl":"https://doi.org/10.1038/s41564-026-02294-7","url":null,"abstract":"Toxoplasma gondii undergoes sexual development exclusively in the feline intestine, a process critical for genetic diversity and population expansion. Recent studies have identified genes critical in suppressing presexual development and metabolic differences in felines that may promote sexual development, but to date, the gene regulatory networks driving development in the cat are unknown. To investigate this, we performed single-cell transcriptomics on parasites isolated from cat intestines, using fluorescent reporter strains and flow cytometry. From 15,068 cells across 2 experiments, we identified rare populations, including cells that bear all of the hallmarks of gametes. Candidate genes emerging from this study were tested via CRISPR-Cas9 perturb-seq, identifying AP2X6 as a regulator of macrogametocyte development. Our single-cell data extend what is known about gene expression changes throughout sexual development and should be useful to those in the field working towards inducing gametogenesis, mating and oocyst production in vitro.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"325 1","pages":""},"PeriodicalIF":28.3,"publicationDate":"2026-04-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147733954","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Nicole S Treichel,Charlie Pauvert,Joana Séneca,Petra Pjevac,David Berry,John Penders,Thomas C A Hitch,Thomas Clavel
{"title":"Benchmarking of shotgun sequencing depth reveals the potential and limitations of shallow metagenomics and strain-level analysis.","authors":"Nicole S Treichel,Charlie Pauvert,Joana Séneca,Petra Pjevac,David Berry,John Penders,Thomas C A Hitch,Thomas Clavel","doi":"10.1038/s41564-026-02334-2","DOIUrl":"https://doi.org/10.1038/s41564-026-02334-2","url":null,"abstract":"Shotgun metagenomics can provide both taxonomic and functional insights, but benchmarking is necessary to determine the sequencing depth appropriate for specific analyses. Here we used complex mixtures of DNA from cultured bacteria and analysed taxonomic composition, strain-level resolution and functional profiles at up to 11 sequencing depths (0.1-50.0 Gb). Reference-based analysis provided accurate strain-level taxonomy at 0.5-1.0 Gb. By contrast, de novo metagenome-assembled genome (MAG) reconstruction required deep sequencing (>10 Gb), and even MAGs deemed high quality by standard metrics were chimeric, with 54.5-81.8% accurately representing original strains, depending on the bioinformatic approach. Functionally, 2 Gb provided reliable insights at the pathway level for each of the mock communities tested, but sufficient proteome coverage was achieved only at or above 10 Gb. Library preparation and host DNA contamination were identified as confounders in shallow metagenomic analysis. This analysis highlights the potential and limitations of shallow metagenomics and provides guidance to accurately capture strain-level diversity using MAGs.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"46 1","pages":""},"PeriodicalIF":28.3,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147731400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Navigating multi-omic integration methods for human microbiome research.","authors":"Efrat Muller,Tal Bamberger,Elhanan Borenstein","doi":"10.1038/s41564-026-02328-0","DOIUrl":"https://doi.org/10.1038/s41564-026-02328-0","url":null,"abstract":"Multi-omic studies in human microbiome research hold great potential for advancing our understanding of host-microbiome interactions. However, despite the growing availability of multi-omic datasets, analysing such data remains a major conceptual, analytical and computational challenge. Introduction of new multi-omic integration methods to address these challenges further complicates researchers' efforts to navigate this expanding field. In this Review, we outline the landscape of multi-omic integration methods in the context of human microbiome research. In contrast to previous reviews, we specifically emphasize the different biological questions addressed by various integration approaches, including questions related to interactions between different molecular layers, molecular shifts that occur in disease, subgrouping of patients based on molecular profiles, and identification of biological mechanisms that underlie such associations. Our aim is to provide a timely, convenient and comprehensive resource for the microbiome research community, allowing researchers to identify the multi-omic integration approach that is best suited to their data and objectives.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"24 1","pages":""},"PeriodicalIF":28.3,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147731333","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Phytophthora targets plant extracellular vesicles to promote infection.","authors":"Yuanpeng Xu,Xiaoying Kong,Qian Qiao,Changhao Liu,Jinyi Zhu,Lei Wang,Yanhao Hu,Yujing Sun,Min Qiu,Wei Yan,Suomeng Dong,Wenbo Ma,Yan Wang,Yuanchao Wang","doi":"10.1038/s41564-026-02325-3","DOIUrl":"https://doi.org/10.1038/s41564-026-02325-3","url":null,"abstract":"Extracellular vesicles (EVs) transport biologically active molecules and are known to mediate host defence against microbial pathogens, including plant fungal pathogens. However, the mechanism by which pathogens disrupt EV-dependent defence remains unclear. Here we show that Phytophthora capsici, a global crop pathogen, counteracts EV-mediated plant defence through targeted lipase activity. We show that Arabidopsis releases EVs containing tetraspanin (TET), specifically TET8- and TET9-EVs, which damage germinated spores of Phytophthora, reducing infection. As a counter-defence, Phytophthora secretes an infection-induced apoplastic lipase, Plant Extracellular Vesicle Destroyer 1 (PED1), which targets TET8- and TET9-EVs. This occurs via interaction with the EV membrane-localized protein Defective Glycosylation 1 (DGL1), which directly interacts and co-localizes with TET8 and TET9 on the EV membrane. PED1 damages TET8- and TET9-EVs through its lipase activity towards campesteryl esters, suppressing EV-mediated plant defence. Our study reveals a mechanism used by Phytophthora to counteract EV-mediated host defence.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"136 1","pages":""},"PeriodicalIF":28.3,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147726220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Ming-Hua Wu,Ya-Nan Lv,Hui Li,Hui Qian,Yun-Yun Wei,Yun-Ran Zhang,Shuang Liang,Xue-Ming Zhu,Jian-Ping Lu,Maurizio Del Poeta,Zong-Hua Wang,Yong-Hwan Lee,Naweed I Naqvi,Richard A Wilson,Daniel J Klionsky,Fu-Cheng Lin,Xiao-Hong Liu
{"title":"MoCox6 is a regulator of mitophagy and a druggable target in Magnaporthe oryzae.","authors":"Ming-Hua Wu,Ya-Nan Lv,Hui Li,Hui Qian,Yun-Yun Wei,Yun-Ran Zhang,Shuang Liang,Xue-Ming Zhu,Jian-Ping Lu,Maurizio Del Poeta,Zong-Hua Wang,Yong-Hwan Lee,Naweed I Naqvi,Richard A Wilson,Daniel J Klionsky,Fu-Cheng Lin,Xiao-Hong Liu","doi":"10.1038/s41564-026-02329-z","DOIUrl":"https://doi.org/10.1038/s41564-026-02329-z","url":null,"abstract":"Mitophagy is a selective autophagic process that maintains cellular homeostasis by degrading damaged mitochondria and is a promising antifungal target. However, few inner mitochondrial membrane (IMM) regulators of mitophagy are known. Here we identify cytochrome c oxidase subunit 6 (MoCox6) as an IMM regulator in Magnaporthe oryzae that binds MoAtg5 and MoAtg14 following outer mitochondrial membrane rupture to mediate mitophagy. MoSirt5 regulates this process by desuccinylating MoCox6 at K144. Structural analysis revealed that residue D95 at the MoSirt5-MoCox6 interface mediates the dual role of MoCox6 in mitophagy and mitochondrial metabolic competence. Deletion of the COX6 gene significantly reduced vegetative growth and virulence in both M. oryzae and Alternaria alternata. Through high-throughput screening, we identified a small-molecule compound, Pan-RAS-IN-1, which targets MoCox6 to inhibit mitophagy, thereby suppressing M. oryzae virulence. Pan-RAS-IN-1 exhibits broad-spectrum antifungal activity, and its application to rice plants significantly suppressed rice blast incidence.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"16 1","pages":""},"PeriodicalIF":28.3,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147726222","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Salmonella-derived haem inhibits macrophage phagocytosis and promotes infection in mice.","authors":"Zuoqiang Wang,Huang Tang,Wanqiu Huang,Chengyue Wang,Yana Chen,Jingchen Yu,Tao Zhou,Bingjie Wen,Jinjing Ni,Danni Wang,Jing Tao,Siqi Zhu,Lin Lyu,Lei Chen,Jun Li,Qihong Kuang,Daojin Yu,Jianping Liu,Lifeng Pan,Mei Zhang,Yue Xu,Guo-Ping Zhao,Jie Lu,Yu-Feng Yao","doi":"10.1038/s41564-026-02341-3","DOIUrl":"https://doi.org/10.1038/s41564-026-02341-3","url":null,"abstract":"Bacterial pathogens such as Salmonella enterica serovar Typhimurium can resist phagocytosis by macrophages. Here we explored the role of bacterial haem biosynthesis in phagocytosis resistance. Using transposon sequencing (Tn-seq) during Salmonella infection of macrophages, we identify a methyltransferase, SirM, that indirectly inhibits phagocytosis of bacteria. Mechanistically, sirM is activated upon interaction with macrophages and methylates HemL, a key enzyme in haem biosynthesis, resulting in upregulation of haem synthesis by Salmonella. Salmonella-derived haem inhibits Cdc42 activation in a Toll-like receptor 4 (TLR4)-dependent manner to inhibit phagocytosis. Moreover, sirM promotes macrophage death by increasing haem synthesis. Experiments in mouse models show that sirM is required for virulence and confers a competitive advantage over intestinal commensal bacteria during infection. We also found that sirM is distributed among enteric pathogens. Collectively, our findings show that bacterial haem promotes evasion of phagocyte responses and pathogenesis to confer an advantage in the host.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"73 1","pages":""},"PeriodicalIF":28.3,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147726221","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Gitta Szabó,Eric Olo Ndela,Sujung Lim,Alireza Saidi-Mehrabad,Brian P Hedlund,Frederik Schulz
{"title":"Hunting for new lineages and mechanisms of life.","authors":"Gitta Szabó,Eric Olo Ndela,Sujung Lim,Alireza Saidi-Mehrabad,Brian P Hedlund,Frederik Schulz","doi":"10.1038/s41564-026-02336-0","DOIUrl":"https://doi.org/10.1038/s41564-026-02336-0","url":null,"abstract":"","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"65 1","pages":""},"PeriodicalIF":28.3,"publicationDate":"2026-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147726219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Faecalibacterium prausnitzii enzyme reprograms PD-L1 trafficking and sensitizes colorectal cancer to immunotherapy in mice.","authors":"Siqi Ji,Yuanhui Liu,Yuejie Xu,Junzhao Gao,Jingzheng Jin,Ping Jiang,Yixuan Li,Dan Su,Yu Zhao,Shuqiao Yang,Shuai Zhang,Wenbiao Shi,Qian Zhou,Mingming Zhang","doi":"10.1038/s41564-026-02326-2","DOIUrl":"https://doi.org/10.1038/s41564-026-02326-2","url":null,"abstract":"Microbiome-host interactions can influence colorectal cancer (CRC) outcomes and the effectiveness of immunotherapy treatment, but the precise mechanisms underlying this are poorly understood. Here we analyse CRC patient cohort data and observe that Facalibacterium prausnitzii abundance in faecal samples correlates with improved CRC survival outcome and immunotherapy response. In vitro assays and experiments in azoxymethane plus dextran sulfate sodium (AOM/DSS) and Apcmin/+ mouse CRC models show that F. prausnitzii extracts have anti-tumour activity. Mass spectrometry identifies F. prausnitzii phosphoribosyl pyrophosphate synthetase (fpPRPS) as a bacterial enzyme that inhibits tumour development and promotes CD8+ T-cell responses. Mechanistically, fpPRPS depletes ATP levels in CRC cells, which then inhibits GTP-GDP exchange on Rab11a, reprogramming CRC energy metabolism. This leads to Rab11a degradation and the disruption of PD-L1 trafficking to reduce the inhibition of T-cell responses. fpPRPS inhibition of tumour progression is PD-L1-dependent. We also show that fpPRPS and anti-PD-1 treatment synergize to promote CD8+ T-cell responses and tumour control in mice. These findings suggest fpPRPS as a potential strategy for sensitizing CRC to immunotherapy.","PeriodicalId":18992,"journal":{"name":"Nature Microbiology","volume":"19 1","pages":""},"PeriodicalIF":28.3,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147702107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}